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宣肺败毒方来源sRNA靶向血管紧张素转换酶改善脂多糖诱导的小鼠急性肺损伤

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高银平, 张金君, 李薇薇, 陈春燕, 张玉莹, 郑涵月, 汪杰, 张晗, 苗琳, 孙娜

中草药 | 药理与临床 2026,57(4): 1336-1349

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中草药 |药理与临床 2026 , 57 (4) : 1336 -1349

宣肺败毒方来源sRNA靶向血管紧张素转换酶改善脂多糖诱导的小鼠急性肺损伤

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高银平, 张金君, 李薇薇, 陈春燕, 张玉莹, 郑涵月, 汪杰, 张晗, 苗琳, 孙娜

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苗琳

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高银平: 高银平，硕士研究生，研究方向为中药学。E-mail:gaoyinping2000@163.com

Xuanfei Baidu Formula derived from sRNA targeting angiotensin-converting enzyme ameliorates lipopolysaccharides-induced acute lung injury in mice

GAO Yinping, ZHANG Jinjun, LI Weiwei, CHEN Chunyan, ZHANG Yuying, ZHENG Hanyue, WANG Jie, ZHANG Han, MIAO Lin, SUN Na

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doi: 10.7501/j.issn.0253-2670.2026.04.013

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目的探讨宣肺败毒方（Xuanfei Baidu Formula，XFBD）来源小RNA（small RNA，sRNA）通过靶向血管紧张素转换酶（angiotensin-converting enzyme，ACE）对脂多糖（lipopolysaccharides，LPS）诱导小鼠急性肺损伤（acute lung injury，ALI）的保护作用及机制。方法采用改良CTAB法提取XFBD的sRNA并建立文库，预测筛选靶向ACE的sRNA。通过双荧光素酶报告系统验证其靶向性，并在人肺微血管内皮细胞（human pulmonary microvascular endothelial cells，HPMEC）中筛选可抑制ACE表达的sRNA。采用ELISA、Western blotting和qRT-PCR检测sRNA对血管紧张素Ⅱ（angiotensin Ⅱ，AngⅡ）生成、核因子-κB抑制蛋白α（inhibitor of nuclear factor-κB α，IκBα）及炎症因子表达的影响。建立LPS诱导的ALI小鼠模型，设置对照组、模型组、卡托普利（10 mg/kg）组、XFBD（9.2 g/kg）组、NC-sRNA（10 nmol/只）组、ACE-sRNA-1（10 nmol/只）组和ACE-sRNA-26（10 nmol/只）组，每组6只。采用苏木素-伊红（hematoxylin-eosin，HE）染色和Micro-CT评估肺组织病理与影像学变化；检测外周血中白细胞数、中性粒细胞数及支气管肺泡灌洗液（bronchoalveolar lavage fluid，BALF）中总蛋白浓度、白细胞、中性粒细胞、淋巴细胞数量；免疫组化法检测肺组织中上皮型钙黏蛋白（vascular endothelial-cadherin，VE-cadherin）和细胞间黏附分子-1（intercellular adhesion molecule-1，ICAM-1）表达；Western blotting和qRT-PCR检测肺组织ACE- Ang Ⅱ-Ang Ⅱ 1型受体（AngⅡ type 1 receptor，AT1R）通路、IκBα及炎症因子表达；ELISA检测血清中Ang II和炎症因子水平。结果从XFBD中筛选出50条潜在靶向ACE的sRNA，经验证26条具有靶向性，其中12条显著抑制HPMEC细胞中ACE表达（P＜0.05、0.01、0.001）。7条sRNA显著抑制Ang Ⅱ生成，以ACE-sRNA-1/26作用最显著（P＜0.001），并可抑制IκBα蛋白及炎症因子表达（P＜0.01、0.001）。动物实验中，模型组小鼠肺损伤严重（P＜0.001）；与模型组比较，ACE-sRNA-1和ACE-sRNA-26显著改善小鼠肺损伤（P＜0.05、0.01、0.001），上调肺组织VE-cadherin表达（P＜0.001），下调肺组织ICAM-1、ACE、AT1R、IκBα和炎症因子表达（P＜0.05、0.01、0.001），同时降低血清Ang II和炎症因子水平（P＜0.05、0.01、0.001）。结论 XFBD来源的ACE-sRNA-1和ACE-sRNA-26能够靶向抑制ACE表达及活性，减轻肺血管内皮炎症和屏障损伤，改善LPS诱导的小鼠ALI，其机制可能与调控ACE-Ang Ⅱ-AT1R通路有关。

关键词

血管紧张素转化酶 / 宣肺败毒方 / sRNA / 急性肺损伤 / 炎症 / 柚皮苷 / 虎杖苷 / 穗花牡荆苷 / 苦杏仁苷 / 甘草酸 / 马鞭草苷 / 芥子碱 / 毛蕊花糖苷 / 甘草苷 / 麻黄碱

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Objective To investigate the protective effect and mechanism of small RNAs (sRNA) derived from Xuanfei Baidu Formula (宣肺败毒方, XFBD) targeting angiotensin-converting enzyme (ACE) in lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Methods The modified CTAB method was employed to extract sRNA from XFBD and a library was constructed, followed by prediction and screening of sRNAs targeting ACE. The targeting specificity was verified using a dual-luciferase reporter system, and sRNAs capable of suppressing ACE expression were screened in human pulmonary microvascular endothelial cells (HPMEC). The effects of sRNA on angiotensin Ⅱ (Ang II) generation, inhibitor of inhibitor of nuclear factor-κB α (IκBα) and inflammatory cytokine expressions were examined by ELISA, Western blotting and qRT-PCR. An LPS-induced ALI mice model was established, control group, model group, captopril (10 mg/kg) group, XFBD (9.2 g/kg) group, NC-sRNA (10 nmol/animal) group, ACE-sRNA-1 (10 nmol/animal) group and ACE-sRNA-26 (10 nmol/animal) group were set up, with six mice in each group. Hematoxylin-eosin (HE) staining and Micro CT were used to evaluate the pathological and imaging changes of lung tissue; The number of white blood cells and neutrophils in peripheral blood, as well as the total protein concentration, white blood cells, neutrophils and lymphocytes numbers in bronchoalveolar lavage fluid (BALF) were detected; Immunohistochemistry was used to detect the expressions of vascular endothelial-cadherin (VE-cadherin) and intercellular adhesion molecule-1 (ICAM-1) in lung tissue; Western blotting and qRT-PCR were used to detect the expressions of ACE-Ang Ⅱ-Ang Ⅱ type 1 receptor (AT1R) pathway, IκBα and inflammatory factors in lung tissue; ELISA was used to detect the levels of Ang II and inflammatory factors in serum. Results A total of 50 potential ACE-targeting sRNAs were screened from XFBD, with 26 sRNAs validated to exhibit targeting effects, among which 12 sRNAs significantly inhibited ACE expression in HPMEC cells (P < 0.05, 0.01, 0.001). Seven sRNAs significantly suppressed Ang II generation, with ACE-sRNA-1/26 demonstrating the most potent effect (P < 0.001), inhibited IκBα protein and inflammatory factor expressions (P < 0.01, 0.001). In animal experiments, mice in model group had severe lung injury (P < 0.001); Compared with model group, ACE-sRNA-1 and ACE-sRNA-26 significantly improved lung injury in mice (P < 0.05, 0.01, 0.001), up-regulated VE-cadherin expression in lung tissue (P < 0.001), down-regulated ICAM-1, ACE, AT1R, IκBα and inflammatory factor expressions in lung tissue (P < 0.05, 0.01, 0.001), and reduced Ang II and inflammatory factor levels in serum (P < 0.05, 0.01, 0.001). Conclusion ACE-sRNA-1 and ACE-sRNA-26 derived from XFBD could target the inhibition of ACE expression and activity, alleviate pulmonary endothelial inflammation and barrier damage, and improve LPS-induced ALI in mice. The mechanism may be related to the regulation of ACE-Ang Ⅱ-AT1R pathway.

Key words

angiotensin-converting enzyme / Xuanfei Baidu Formula / sRNA / acute lung injury / inflammation / naringin / polydatin / agnuside / amygdalin / glycyrrhizic acid / cornin / sinapine / verbascoside / liquiritin / ephedrine

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高银平, 张金君, 李薇薇, 陈春燕, 张玉莹, 郑涵月, 汪杰, 张晗, 苗琳, 孙娜. 宣肺败毒方来源sRNA靶向血管紧张素转换酶改善脂多糖诱导的小鼠急性肺损伤. 中草药, 2026 , 57 (4) : 1336 -1349 . DOI: 10.7501/j.issn.0253-2670.2026.04.013

GAO Yinping, ZHANG Jinjun, LI Weiwei, CHEN Chunyan, ZHANG Yuying, ZHENG Hanyue, WANG Jie, ZHANG Han, MIAO Lin, SUN Na. Xuanfei Baidu Formula derived from sRNA targeting angiotensin-converting enzyme ameliorates lipopolysaccharides-induced acute lung injury in mice[J]. Chinese Traditional and Herbal Drugs, 2026 , 57 (4) : 1336 -1349 . DOI: 10.7501/j.issn.0253-2670.2026.04.013

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天津市教委科研计划项目 (2023KJ139)

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2026年第57卷第4期

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doi: 10.7501/j.issn.0253-2670.2026.04.013

接收时间：2025-09-12
首发时间：2026-09-09

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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